Chronic Kidney DiseaseCRIB-DONOR IINCT02973607
Effects of a Reduction in Renal Function on Cardiovascular Structure and Function
An observational study of Chronic Kidney Disease and Hypertrophy, Left Ventricular, run by University Hospital Birmingham NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Chronic kidney disease (CKD) is present in 1 in 7 of the population and confers a high risk of cardiovascular disease. The pathophysiology of cardiovascular disease in CKD is poorly understood because CKD is always accompanied by confounding factors including the underlying disease process (e.g. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Disease, Hypertrophy, Left Ventricular, Hypertension
- What is being tested?
- Nephrectomy
- Type of treatment
- Surgery or procedure
- How many people
- 95 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 23 May 2017to 31 Jul 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Living donors and healthy controls
Who may be able to join
- All patients who took part in the original CRIB-Donor study.
Who cannot join
- Pregnant women
- Patients will have previously met nationally set criteria for living donation which excludes those with:
- Diabetes mellitus Atrial fibrillation Left ventricular dysfunction (ejection fraction <40% on transthoracic echocardiography) History of cardiovascular or pulmonary disease Evidence of hypertensive end-organ damage.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Queen Elizabeth Hospital Birmingham
Birmingham, West Midlands, B15 2TH
About this study
Official title: Effects of a Reduction in Renal Function on Cardiovascular Structure and Function: A 5 Year Study of Kidney Donors.
Chronic kidney disease (CKD) is present in 1 in 7 of the population and confers a high risk of cardiovascular disease. The pathophysiology of cardiovascular disease in CKD is poorly understood because CKD is always accompanied by confounding factors including the underlying disease process (e.g. diabetes mellitus, systemic vasculitis) and the consequences of CKD including hypertension, anaemia and inflammation.
Nephrectomy in kidney donors causes a 30% reduction in renal function providing an ideal study population to measure prospectively the effects of reduced kidney function on the cardiovascular system.
The CRIB-Donor study (ClinicalTrials.gov Identifier:NCT01028703) demonstrated adverse effects on cardiovascular structure and function at 12 months compared to controls including an increase in left ventricular mass. This proposal will measure the changes in cardiovascular structure and function, cardiovascular age and biochemical changes at 5 years providing information on the long term effects of reduced renal function.
Read the detailed description
A reduction in renal function at one year in kidney donors is associated with adverse cardiovascular structural and functional changes. Increases in LV mass and perhaps fibrosis along with increased arterial stiffness are associated with adverse changes in prognostic imaging biomarkers and may in the long term contribute to the development of clinical disease such as heart failure and arrhythmia.
It is important to follow this valuable and well characterised cohort of subjects to investigate the further natural history of these cardiovascular effects and determine whether such changes tend to regress, stabilise or worsen over time.
Hypotheses:
The reduction in GFR occurring after surgical uni-nephrectomy in donors is associated with long term adverse cardiac and vascular effects which include:
- A sustained increased in left ventricular mass, impaired left ventricular systolic and diastolic function and increased left ventricular interstitial fibrosis.
- Reduced aortic distensibility.
- Increased systolic but not diastolic blood pressure.
- Increases in oxidative stress, inflammation and collagen turnover
- Cardiovascular ageing as evidenced by adverse effects on telomere length and DNA damage.
Study design:
We aim to follow up all 124 patients who originally took part in the CRIB-DONOR study at 5 years and eventually 10 years post nephrectomy.
Statistics and sample size:
Using the effect sizes and variances from our previous work (change in LV mass 7g, SD of change 10g) we calculate that by studying 50 subjects in each group we will have 93% power to detect a difference in LV mass of 7g with an alpha value of 0.05. Due to the nature of a follow up study some drop out can be expected. A minimum of 34 patients is required in each group in order to achieve an 80% power. This effect is clinically important; a fall in LV mass index of one SD has been shown to be associated with a 38% reduction in cardiovascular mortality.
With respect to telomere shortening, assuming mean and SD of base pair length of 5500 and 530 the study will be able to detect a difference of 0.612 SD, i.e. 324 base pairs. A sample size of 50 patients per group would provide a 85% power to detect a difference.
- Being tested
- Nephrectomy
- Medical subject headings
- Renal Insufficiency, Chronic, Hypertrophy, Left Ventricular, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NephrectomyProcedure or surgery
This is observational in design.
| Study group | Role | What they receive |
|---|---|---|
| Donors | Patients who donated a kidney and took part in the original CRIB-DONOR study. Receives: Procedure: Nephrectomy | |
| Controls | Healthy subjects who took part in the original CRIB-DONOR study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular mass and interstitial fibrosis
Measured by CMR (part 1 of study).
Measured: 3 years
Secondary outcomes (4)
Aortic compliance
Measured by CMR (part 1 of study).
Measured: 3 years
Cardiovascular age
Measured by telomere length and studies of DNA damage (part 1 and 2 of study).
Measured: 3 years
Oxidative stress, inflammation and collagen turnover
Measured by assay and bioassay (part 1 of study).
Measured: 3 years
Blood pressure
Measured by ambulatory blood pressure monitoring (part 1 of study).
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2016 (estimated)
- Study start23 May 2017
- Primary completion20 Mar 2020
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anna Price, University Hospital Birmingham NHS Foundation Trust
- Investigators
- Professor John Townend, MbChB, Principal investigator, University Hospital Birmingham NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02973607
- Sponsor's protocol ID
- RRK5913
- Acronym
- CRIB-DONOR II
- Status last verified
- Oct 2018
- First submitted
- 22 Nov 2016
- Last updated
- 5 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of a Reduction in Renal Function on Cardiovascular Structure and Function: A 5 Year Study of Kidney Donors.
- ClinicalTrials.gov ID
- NCT02973607
- Acronym / sponsor ID
- CRIB-DONOR II / RRK5913
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- University Hospital Birmingham NHS Foundation TrustUniversity, hospital or other
- Study start
- 23 May 2017 (actual)
- Primary completion
- 20 Mar 2020 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 25 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic kidney disease (CKD) is present in 1 in 7 of the population and confers a high risk of cardiovascular disease. The pathophysiology of cardiovascular disease in CKD is poorly understood because CKD is always accompanied by confounding factors including the underlying disease process (e.g. diabetes mellitus, systemic vasculitis) and the consequences of CKD including hypertension, anaemia and inflammation.
Nephrectomy in kidney donors causes a 30% reduction in renal function providing an ideal study population to measure prospectively the effects of reduced kidney function on the cardiovascular system.
The CRIB-Donor study (ClinicalTrials.gov Identifier:NCT01028703) demonstrated adverse effects on cardiovascular structure and function at 12 months compared to controls including an increase in left ventricular mass. This proposal will measure the changes in cardiovascular structure and function, cardiovascular age and biochemical changes at 5 years providing information on the long term effects of reduced renal function.
Detailed description
A reduction in renal function at one year in kidney donors is associated with adverse cardiovascular structural and functional changes. Increases in LV mass and perhaps fibrosis along with increased arterial stiffness are associated with adverse changes in prognostic imaging biomarkers and may in the long term contribute to the development of clinical disease such as heart failure and arrhythmia.
It is important to follow this valuable and well characterised cohort of subjects to investigate the further natural history of these cardiovascular effects and determine whether such changes tend to regress, stabilise or worsen over time.
Hypotheses:
The reduction in GFR occurring after surgical uni-nephrectomy in donors is associated with long term adverse cardiac and vascular effects which include:
- A sustained increased in left ventricular mass, impaired left ventricular systolic and diastolic function and increased left ventricular interstitial fibrosis.
- Reduced aortic distensibility.
- Increased systolic but not diastolic blood pressure.
- Increases in oxidative stress, inflammation and collagen turnover
- Cardiovascular ageing as evidenced by adverse effects on telomere length and DNA damage.
Study design:
We aim to follow up all 124 patients who originally took part in the CRIB-DONOR study at 5 years and eventually 10 years post nephrectomy.
Statistics and sample size:
Using the effect sizes and variances from our previous work (change in LV mass 7g, SD of change 10g) we calculate that by studying 50 subjects in each group we will have 93% power to detect a difference in LV mass of 7g with an alpha value of 0.05. Due to the nature of a follow up study some drop out can be expected. A minimum of 34 patients is required in each group in order to achieve an 80% power. This effect is clinically important; a fall in LV mass index of one SD has been shown to be associated with a 38% reduction in cardiovascular mortality.
With respect to telomere shortening, assuming mean and SD of base pair length of 5500 and 530 the study will be able to detect a difference of 0.612 SD, i.e. 324 base pairs. A sample size of 50 patients per group would provide a 85% power to detect a difference.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donors | – | Procedure: NephrectomyPatients who donated a kidney and took part in the original CRIB-DONOR study. |
| Controls | – | –Healthy subjects who took part in the original CRIB-DONOR study. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Living donors and healthy controls
Key inclusion criteria (1 listed)
- All patients who took part in the original CRIB-Donor study.
Key exclusion criteria (3 listed)
- Pregnant women
- Patients will have previously met nationally set criteria for living donation which excludes those with:
- Diabetes mellitus Atrial fibrillation Left ventricular dysfunction (ejection fraction <40% on transthoracic echocardiography) History of cardiovascular or pulmonary disease Evidence of hypertensive end-organ damage.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NephrectomyThis is observational in design. | Procedure or surgery | Donors |
Primary outcome
Left ventricular mass and interstitial fibrosis
Time frame: 3 years
Measured by CMR (part 1 of study).
4 secondary outcomes
Aortic compliance
Time frame: 3 years
Cardiovascular age
Time frame: 3 years
Oxidative stress, inflammation and collagen turnover
Time frame: 3 years
Blood pressure
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Professor John Townend, MbChB principal investigator
University Hospital Birmingham NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Kidney Disease and Hypertrophy, Left Ventricular, run by University Hospital Birmingham NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left ventricular mass and interstitial fibrosis (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2020.